1-hydroxy-3,3-dimethylbutan-2-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 174 g (2 moles) of morpholine were added dropwise to a solution of 232 g (2 moles) of hydroxy-pinacolone and 132 g (2 moles) of malonic acid dinitrile in 500 ml of dimethylformamide, while cooling, in a manner such that the internal temperature did not rise above 40° C. After the reaction had ended, the reaction mixture was stirred into 5 liters of ice-water. The solid product which thereby precipitated was filtered off, washed with water and dried. 170 g of 2-amino-3-cyano-4-tert.-butyl-furan of melting point 86° C. were obtained in this manner. while cooling, in a manner such that the internal temperature did not rise above 40° C The solid product which thereby precipitated was filtered off washed with water dried

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dissolve sodium hydride (380 mg, 9.5 mmol) in anhydrous DMF (7 mL). Cool at 0° C., add dropwise 1-hydroxy-3,3-dimethylbutan-2-one (1.1 g, 9.5 mmol) and stir at this temperature for 30 min. Add a solution of 6-bromo-nicotinonitrile in DMF (7 mL) and heat at 70° C. overnight. Cool the reaction mixture with ice/water and work-up sequentially with EtOAc and water. Dry the organic fraction over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (4:1) to obtain the desired intermediate (424 mg, 50%). MS (ES+) if/A: 219 (M+H)+. heat at 70° C. overnight Dry the organic fraction over MgSO4 filter concentrate in vacuo Purify by chromatography on silica gel eluting with hexane/EtOAc (4:1)